This invention relates to a method for the synthesis of nojirimycin derivatives and, more particularly, to the synthesis of deoxynojirimycin and nojirimycin .delta.-lactam from an epoxide derivative of L-idofuranose.
Deoxynojirimycin is a well-known glucosidase inhibitor [Ishida et al., J. Antibiot. Ser. A20, 66 (1967)]. Recently, it has been suggested as having potential use for the treatment of acquired immune deficiency syndrome (AIDS). See, e.g., Sunkara et al., Biochem. Biophys. Res. Commun. 148(1), 206-210 (1987); Tyms et al., Lancet, Oct. 31, 1987, pp. 1025-1026; Walker et al., Proc. Natl. Acad. Sci. U.S.A. 84, 8120-8124 (1987); and Gruters et al., Nature 330, 74-77 (1987).
Derivatives of deoxynojirimycin also have been reported to have potential use as anti-AIDS drugs based on inhibitory activity against human immunodeficiency virus (HIV). See, e.g., the report of such use of the N-methyl derivative of deoxynojirimycin in PCT Inter. Appln. WO 87/03903, published July 2, 1987, and the substantially more effective anti-HIV activity of the N-butyl derivative of deoxynojirimycin as disclosed in U.S. Pat. No. 4,849,430.
The properties of deoxynojirimycin as a glucosidase inhibitor and the recognition of the potential applications of such compounds have led to considerable studies on the synthesis of nojirimycin derivatives. See, e.g., Paulsen et al., Chem. Ber. 100, 802 (1967); Kinast and Schedel, Angew. Chem. Int. Edit. 20, 805 (1981); Vasella and Voeffray, Helv. Chim. Acta 65, 1134 (1982); Bernotas and Ganem, Tetrahedron Lett. 26, 1123 (1985). Although the most common strategy for the synthesis of nojirimycin derivatives has been by the introduction of nitrogen with retention of configuration at C-5 of glucose [Saeki and Ohki, Chem. Pharm. Bull. 16, 2477 (1968); Sohmidt et al., Liebigs Ann. Chem. 1989, 423], the only reported stereospecific synthesis of nojirimycin .delta.-lactam was by hypoiodite oxidation of nojirimycin [Inouye et al., Tetrahedron 24, 2125 (1968)].